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Slide 1: NIH Symposium: Why Do We Get It Wrong? Methods of Oncology
BioMarker Validation: Trying to Get it Right!
Daniel F. Hayes, M.D.
Slide 2: ASCO Tumor Marker Guidelines Panel
- ER, PgR Select Endocrine Therapy
- HER2 Select Trastuzumab
- CA15-3, CA27.29, CEA Monitor Selected Pts with Metastatic
Disease
Slide 3: ASCO Tumor Marker Guidelines
- Why Are the Guidelines So Conservative?
- Only recommended markers for which results would change clinical
decisions
- Evidence-based
- Lack of Level of Evidence I or II studies:
- A Tumor Marker Utility Grading Scale
Slide 4: TMUGS: Levels of Evidence
Level Definition
- Prospective, Marker Primary Objective, Well-powered OR
Meta-analysis
- Prospective, Marker Secondary Objective
- Retrospective, Outcomes, Multivariate Analysis
- Retrospective, Outcomes, Univariate
- Retrospective, Correlation with Other Marker, No Outcomes
Slide 5: TMUGS: Levels of Evidence
Level Definition
- Prospective, Marker Primary Objective, Well-powered OR
Meta-analysis
- Prospective, Marker Secondary Objective
- Retrospective, Outcomes, Multivariate Analysis
- Retrospective, Outcomes, Univariate
- Retrospective, Correlation with Other Marker, No Outcomes
Slide 6: When is a Marker Clinically Useful?
- It is either prognostic or predictive
- The magnitude of effect is sufficiently large that clinical decisions
based on the data result in outcomes that are acceptable
- Greater chance for benefit
- Smaller toxicity risk
- The estimate of magnitude of effect is reliable
- Assay is reproducible
- Clinical trial/marker study design is appropriate
- Results are validated in subsequent well-designed studies
Slide 7: Pure Prognostic Factors (Chart)
Slide 8: Prognostic Factors: Clinical Utility
How much added benefit is required to justify treatment?
- Depends on toxicity of treatment
- Depends on perspective of patients
Slide 9: Pure Predictive Factor (for Sensitivity to Therapy) (CHART)
Slide 10: Tamoxifen vs. not recurrence effect of EF (Two Charts POOR
AND POSITIVE)
Slide 11: Tumor Marker Validation
- Examples: Breast Cancer (TABLE)
Slide 12: Tumor Marker Validation
- Examples: Breast Cancer (TABLE)
Slide 13: Oncotype DX 21 Gene Recurrence Score (RS) Assay
16 CANCER AND 5 reference genes from 3 studies (chart)
Slide 14: NSABP: Clinical Validation Study of Oncotype DX (CHART)
- NSABP 20: Node Neg, ER+, Tam treated patients
- 10 yr Distant Recurrence (CHART)
Slide 15: NSABP B-14 Clinical Validation Study of Oncotype DX
- NSABP 14: Node Neg, ER+, Tam treated patients
- Tam treated patients: 10 year Distant Recurrence (CHART)
Slide 16: Proposed US Breast Intergroup Trial (Flow Chart)
Slide 17: Conclusions
- Many proposed tumor markers
- Most studies are LOE III or worse
- Cooperative Groups are now performing LOE II associated with
prospective therapeutic clinical trials
- New Cooperative Group studies will be LOE I
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